Applications of macrocyclic metal complexes are numerous. In the field of artificial metallonucleases, it's a challenge to cleave DNA or RNA at specific site for further development in genetic engineering. To achieve this goal, it is very important to understand interactions of metal complexes with large structured RNA or DNA molecule, which are dependent on the selective binding of metal complexes to specific RNA or DNA sites and subsequent hydrolysis reactions. In this regards, the macrocyclic ligands and their substituents play a key role in providing specific binding with nucleic acids (DNA or RNA molecules) and hydrolysis reactions (Bridger, G. J. et. al, J. Med. Chem. 1999, 42, 3971-81; New, K. et al., J. Am. Chem. Soc. 2008, 130, 14861-71; Rossiter, C. S. et al., J. Inorg Biochem 2009, 103, 64-71; Chang C. A. et al., Inorg. Chem. 2005, 44, 6646-54). Macrocyclic ligands also play an important role in the field of nuclear medicine by forming stable metal complexes with various radionuclei (WO2011031073). Tetraaza complexes formed between linear or macrocyclic amines and radioactive rhodium-105 have been used in diagnostics and therapeutics (Bounsall, E. J. et al., Canadian J. of chemistry 1970, 48, 1481; U.S. Pat. No. 5,489,425). A cobalt complex, [Co(III)(cyclen)Cl2]Cl, has been found to be selectively cytotoxic to human leukemia cells (He, Z. et al., J. Pharmacology 2010, 637, 11-15). In medical diagnostics, macrocyclic ligand-metal complexes have been widely used as contrast agents (WO2011031073; U.S. Pat. No. 5,482,699; U.S. Patent Application Publication 2011/0177002). For example, a 64Cu-tetraaza complex has been used for imaging tumor U87MG, and tetraaza-99mTc complexes have been used in diagnostics (Cai, W. et al., Eur. J. Nucl. Med. Mol. Imaging. 2007, 34, 850-858; Troutner, D. E. et al., J Nucl Med 1980, 21, 443-448). Furthermore, many gadolinium complexes have been commercialized with trade names, Magnevist, MultiHance, Omniscan, OptiMARK, ProHance, and Dotarem, as magnetic resonance imaging (MRI) contrast agents for diagnostics in daily practice (Caravan, P. et al., Chem. Rev. 1999, 99, 2293-2352; Kumar. K. et al., Inorg. Chem. 1993, 32, 4193-4199). Among these, ProHance and Dotarem are tetraaza-based (e.g. DO3A and DOTA) macrocyclic ligands. In the case of prodrug-procontrast, macrocyclic ligand-metal complexes can deliver prodrugs into the targeted cancer cells, thus reducing the toxic dose of active drugs. Simultaneously, they also act as contrast agents allowing the measurement of drug activity in the body. The efficiency of the whole process is dependent on the metal complexes and ultimately on the ligands employed (Frullano, L. et al., Inorg. Chem. 2006, 45, 8489-8491).
Accurate diagnosis needs effective imaging outcome, which is dependent on the characteristics of contrast agents and ultimately is dependent on the characteristics of ligands. Therefore, there remains a need in developing novel ligands for better imaging in MRI studies to avoid confusing situations in identification, investigation and effective treatment of diseases. In artificial metallonuclease or fluorescence probe areas, it is also essential to develop novel ligands to effectively cleave nucleic acid at a desirable site or to function as efficient fluorescence probes.